This proposal addresses a need for an improved technology for both screening and treatment of patients with cystic neoplasms of the pancreas. Currently, percutaneous and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) technology is used as a first line of diagnosis for pancreatic lesions. However, the complex regional anatomy of the pancreas and the very difficult differentiation between various cystic lesions make the diagnosis of pancreatic cysts in general and the distinction between benign and malignant cysts in particular difficult without exploratory surgery. Physical Sciences Inc. (PSI) proposes to develop a technology that will significantly increase the diagnostic accuracy of the EUS-FNA procedures and will also provide a therapeutic option. The diagnostic accuracy will be significantly increased by adding a new micron-scale high resolution optical coherence tomography (OCT) imaging capability to the current routine EUS-guided FNA procedure. A laser therapeutic capability will be implemented. Both, imaging and therapy, will be performed simultaneously thorough the same catheter. We hypothesize that the high resolution imaging capability will not allow only to distinguish between non-neoplastic pseudocysts, the most common cyst in the pancreas, and neoplastic cysts, but will also allow to distinguish the type of lining epithelium (serous versus mucinous as well as benign versus malignant). The laser therapeutic capability will allow thermal coagulation (necrosis) of the diseased epithelial tissue layer of the ore-invasive malignant lesions. With the laser therapy and OCT imaging combined, the dual capability system will have the potential for performing both diagnosis and real-time monitoring of therapy at the micron scale. None of these features are currently available to the physician. In Phase I a benchtop system that will incorporate both OCT and laser ablation will be developed and an in vitro clinical study on pancreatic tissue specimens will be conducted to demonstrate the capability of the system to diag- nose and to ablate the epithelial layer of the cystic neoplasms of the pancreas. Phase II of the project will focus on the development of a clinical portable system that can be used in correlation with current EUS-FNA systems. In Phase II, a pilot clinical study on patients will be performed at the Massachusetts General Hospital to prove the effectiveness of the instrument in cancer staging. An animal study will be performed as well to test the efficiency of laser therapy.